Mechanistic insights into neuronal oscillatory activity in the dopamine-intact and dopamine-depleted primary motor cortex

Student thesis: Doctoral ThesisDoctor of Philosophy

View graph of relations Save citation


Nicholas Johnson


In Parkinson’s disease (PD) the loss of the neurotransmitter dopamine (DA) results in abnormal oscillations of the cortico-basal ganglia network, the emergence of which correlate with symptoms. Increased oscillatory power in the primary motor cortex (M1) is reduced by dopamine replacement therapy and by targeted stimulation, suggesting that M1 plays an important role in the pathology of PD. In this study we have investigated, using pharmacology, the mechanisms by which oscillatory activity in rat M1 is generated and determined the power changes associated with DA depletion and DA receptor modulation.

Extracellular local field potential recordings were made in brain slices of M1 which were prepared using a modified protocol to improve viability. Co-application of carbachol (5 μM) and kainic acid (100 nM) elicited simultaneous theta (4-8 Hz) and gamma (30-40 Hz) oscillations in layer V of M1. These oscillations displayed phase-amplitude coupling; the first report of such findings in vitro. These oscillations were found to be pharmacologically distinct with theta oscillations generated by intrinsic non-synaptic mechanisms while gamma oscillations required contributing excitatory and inhibitory networks.

Following successful unilateral lesions using 6-hydroxydopamine (6-OHDA), as determined by the adjusting step test, DA-depleted (ipsilateral) and DA-intact (contralateral) slices were obtained. Although no difference in the oscillatory profile of M1 ipsilateral, contralateral or age-matched control (AMC) slices was found, bath application of DA reduced gamma power only in the ipsilateral slices and amphetamine only decreased gamma power in contralateral slices. Furthermore, D2-like receptor activation consistently increased both theta and gamma power in contralateral and AMC slices, while only theta power was increased in ipsilateral slices. Overall, these data suggest that DA, through action at multiple sites, differentially modulates the power of both theta and gamma oscillations in M1.

Using the 6-OHDA model, the oscillatory activity of M1 in vivo was investigated. Successful lesions were determined by using the rotometer, the locomotor activity and the adjusting stepping tests at 2-4 weeks post-surgery. Further testing at 22 weeks post-surgery indicated the long-term stability of the lesions. Using depth electrode and EEG recordings, oscillatory activity in the 2-10 Hz range was found in the ipsilateral and contralateral hemispheres of both lesioned and sham animals. However, only in the ipsilateral hemisphere of DA-depleted animals did we detect a 30-40 Hz oscillatory peak, which was localised to layer V of M1. In EEG recordings this led to a significant increase in the interhemispheric ratio. Using depth electrode recordings, the ipsilateral 30-40 Hz oscillation (but not 2-10 Hz oscillation) was reduced by the administration of L-DOPA (6 mg/kg) with a reduction in interhemispheric ratio. However, administration of zolpidem (0.3 mg/kg), which previously reduced abnormal beta oscillatory activity in vivo and in vitro resulting in the rebalancing of interhemispheric beta power (Hall et al., 2014; Prokic et al., 2015), was without effect.

Overall, these studies demonstrate that M1 alone can generate multiple, pharmacologically distinct, but interacting oscillations, which contribute to pathological activity in the DA-depleted state.


Original languageEnglish
Awarding Institution
Award date2 Mar 2017


  • Parkinson’s disease, motor cortex, oscillations, theta, gamma

If you have discovered material in the Aston Research Explorer, which is unlawful e.g. breaches copyright, (either theirs or that of a third party) or any other law, including but not limited to those relating to patent, trademark, confidentiality, data protection, obscenity, defamation, libel, then please read our Takedown Policy and contact the service immediately.

Download statistics

No data available

Employable Graduates; Exploitable Research

Copy the text from this field...